Strategic Alliances

Business development is integral to our mission of building a leading and independent biopharmaceutical company based upon RNAi therapeutics. We aim to identify partners with whom we can advance RNAi therapeutics either in direct collaboration, or through licensing of our products or our intellectual property.

Our business development strategy is to form partnerships that create significant value for ourselves and our partners in the advancement of RNAi therapeutics as a new class of innovative medicines. Specifically, we aim to retain certain development and commercial rights in North America and Europe, while forming partnerships with leading, innovative companies for commercialization of these products in the rest of world. In early 2014, we formed a transformational alliance with Genzyme, a Sanofi company, to develop and commercialize our Genetic Medicine Strategic Therapeutic Area (STAr) up until 2020, principally in territories outside of North America and Europe. Alnylam is also committed to providing licenses to its IP and technology to companies focused on developing RNAi therapeutics for targets outside the company’s core interests and also to companies developing RNAi-based products in other non-strategic areas.

A summary of select business alliances is provided below, in chronological order.

The Alpha-1 Project

In June 2014, we entered into a collaboration with and The Alpha-1 Project (TAP), the venture philanthropy subsidiary of the Alpha-1 Foundation, for the continued advancement of ALN-AAT. TAP’s mission is to work with patients, academia, pharmaceutical and biotech companies, and public health organizations in the pursuit of cures and therapies for chronic obstructive pulmonary disease (COPD) and liver disease caused by AAT deficiency. TAP is partially funding research activities for ALN-AAT.

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Genzyme, a Sanofi Company

In October 2012, Alnylam and Genzyme, a Sanofi company, formed an exclusive alliance to develop and commercialize RNAi therapeutics targeting transthyretin (TTR) for the treatment of transthyretin-mediated amyloidosis (ATTR) in Japan and other Asia-Pacific countries. In January 2014, Alnylam and Genzyme extended this relationship by forming a transformational alliance focused on the advancement of RNAi therapeutics as genetic medicines. Genzyme becomes Alnylam’s geographic partner for its Genetic Medicine STAr up until 2020. Specifically, we retain development and commercial rights in North America and Europe, while Genzyme obtains rights for the Alnylam pipeline programs in rest of world. As part of the new alliance, Alnylam and Genzyme have agreed to co-develop and co-commercialize the revusiran program for cardiac TTR amyloidosis. The companies have also agreed to additional co-development/co-commercialization and global product rights for Genzyme under certain conditions. The alliance is intended to significantly expand and accelerate the global product value for Alnylam’s Genetic Medicine STAr. As part of the new partnership, which is valued at well over billion, Genzyme purchased 0 million in Alnylam stock at a price of approximately /share, representing a 27% premium. In addition, Alnylam is eligible to receive R&D funding, milestone payments, and double-digit royalties. Amongst other objectives, the strategic alliance serves to significantly bolster Alnylam’s balance sheet, enabling increased investment in its RNAi therapeutics pipeline. The alliance excludes all Alnylam RNAi therapeutic programs outside the Genetic Medicine STAr, such as those in its Cardio-Metabolic and Hepatic Infectious Disease STArs, amongst other potential fields.

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Merck

In January 2014, Alnylam agreed to acquire Merck’s wholly owned subsidiary Sirna Therapeutics, Inc., comprising intellectual property and RNAi assets including pre-clinical therapeutic candidates, chemistry, siRNA-conjugate and other delivery technologies.. Merck and Sirna’s delivery technologies complement and extend Alnylam’s own progress and continued focus on RNAi therapeutics, including siRNA-GalNAc conjugates. Under the terms of the agreement, Alnylam payed Merck 5 million in upfront consideration, including 0 million in Alnylam stock and million in cash. In addition, Alnylam will pay future milestones and royalties to Merck in association with certain products that are advanced using Merck technology and IP.

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The Medicines Company

In February 2013, The Medicines Company and Alnylam announced an exclusive global alliance to advance the ALN-PCS program. The collaboration includes ALN-PCS02 an intravenously administered RNAi therapeutic which has completed a Phase 1 trial, and ALN-PCSsc a subcutaneously administered RNAi therapeutic currently in pre-clinical development. Alnylam will continue development of the program while funded by The Medicines Company to complete certain pre-clinical and Phase 1 clinical studies. The Medicines Company will then lead and fund development from Phase 2 forward and commercialize the ALN-PCS program if successful. In November 2013, Alnylam and The Medicines Company announced the selection of a Development Candidate for ALN-PCSsc, a GalNAc-siRNA targeting PCSK9 enabling SC delivery, and provided guidance that the companies intend to file an IND or IND equivalent by the end of 2014 or early 2015.

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Monsanto

In August 2012, Alnylam and Monsanto formed a strategic alliance to advance biological technologies in the field of agriculture. Under the terms of the agreement, Monsanto receives worldwide, exclusive rights to use our RNAi platform technology and IP in the field of agriculture, including the ability to grant sublicenses. The agreement also includes the transfer of technology from Alnylam to Monsanto and a collaborative research project. In addition, Monsanto becomes our strategic partner in agriculture for a 10-year period.

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Ascletis Pharmaceuticals

In July 2012, Ascletis received an exclusive license from Alnylam to develop and commercialize ALN-VSP in China including Hong Kong, Macau, and Taiwan. The focus will be on advancing ALN-VSP into a Phase 2 study for the treatment of HCC. We will retain all rights in the rest of the world, and are eligible to receive milestones and royalties based on product sales. In addition, we may use the data generated in China by Ascletis under this strategic collaboration for development of ALN-VSP in the rest of the world.

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Arrowhead Research Corporation

In January 2012, Alnylam granted Arrowhead a non-exclusive license under its intellectual property that enables the discovery, development, and commercialization of an RNAi therapeutic targeting the hepatitis B virus (HBV). We are eligible to receive from Arrowhead milestone payments and royalties on sales of product resulting from the license. In addition, we have received a license from Arrowhead to utilize their Dynamic Polyconjugate (DPC) delivery technology for an RNAi therapeutic product. Arrowhead is eligible to receive from Alnylam milestone payments and royalties on sales of product resulting from the license.

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Kyowa Hakko Kirin Co., Ltd.

In June 2008, Alnylam and Kyowa Hakko formed an exclusive alliance to develop and commercialize ALN-RSV01, an RNAi therapeutic in clinical development for the treatment of respiratory syncytial virus (RSV) infection, in Japan and other major markets in Asia. The partnership also includes additional RSV-specific RNAi therapeutic compounds that comprise the ALN-RSV program.

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Takeda Pharmaceutical Company Limited

In May 2008, Alnylam and Takeda formed a strategic platform alliance that provides Takeda with broad, worldwide, non-exclusive access to and enablement with our RNAi therapeutics platform technology and intellectual property in the fields of oncology and metabolic disease. This landmark alliance was the first major RNAi therapeutics partnership between a Japanese pharmaceutical company and a U.S. biotechnology company.

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Regulus Therapeutics

In 2007, Alnylam and Isis created Regulus, the leading microRNA therapeutics company. Isis and Alnylam scientists and collaborators were the first to discover microRNA antagonist strategies that work in vitro and in vivo in animal studies (Krutzfeldt et al. (2005) Nature 438, 685-689; Esau et al. (2006) Cell Metab., 3, 87-98). Isis and Alnylam created and consolidated key IP believed by the companies to be required for development and commercialization of microRNA therapeutics.

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Novartis AG

In September 2005, Alnylam and Novartis Institute for BioMedical Research (NIBR), the research institute of Novartis AG, formed a landmark RNAi therapeutics alliance. The 5-year collaboration, completed in 2010, resulted in the selection by Novartis of 31 gene targets for further development of RNAi therapeutics. In return, we are entitled to receive significant milestone payments upon achievement of certain specified development and annual net sales events for any RNAi therapeutic products developed.

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Medtronic, Inc.

In early 2005, Alnylam and Medtronic formed a partnership to develop ALN-HTT, an RNAi therapeutic drug-device combination therapy for the treatment of Huntington’s disease. Medtronic is advancing the ALN-HTT program, and Alnylam will supply drug product to Medtronic and is entitled to receive milestones and royalty payments on future annual net sales.

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Isis Pharmaceuticals, Inc.

In March 2004 and as further extended in 2009, Alnylam entered into a broad, strategic collaboration and license agreement with Isis, a leading developer of single-stranded antisense oligonucleotide drugs. The agreement enhances our intellectual property position with respect to RNAi-based therapeutics. Specifically, Isis granted Alnylam licenses to its current and future patents and patent applications relating to oligonucleotide chemistry and to RNA-targeting mechanisms for the research, development and commercialization of RNAi therapeutics.

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In addition, we have an effort focused on out-licensing our RNA IP estate to enable other companies to advance products and technologies that are complementary to our business, including other human therapeutics or other businesses such as biologics manufacturing or agriculture.

In addition to forming strategic alliances with major pharmaceutical and top-tier biotechnology companies, we are committed to enabling the broader biomedical industry with access to our IP by offering target-specific therapeutic licenses in areas outside our strategic focus through our InterfeRx™ program. To that end we have issued licenses to the following companies:

Sylentis, S.A.;

Tekmira Pharmaceuticals Corp.;

Calando Pharmaceuticals, Inc. (a subsidiary of Arrowhead Research);

Quark Pharmaceuticals, Inc.;

Benitec, Ltd.; and

GeneCare Research Institute Co., Ltd.

We also offer non-therapeutic license agreements to life science reagent and service providers, and have agreements with a variety of companies and institutions, including:

Invitrogen;

Applied Biosystems (formerly Ambion);

Sigma (formerly Proligo);

Qiagen; IDT;

Cenix Biosciences;

Cell Signaling;

Eurogentec;

Dharmacon (a division of Thermo Fisher Scientific);

Bio-rad;

Hayashi;

GeneDesign;

GenePharma; and,

KOKEN

Since Alnylam’s inception in 2002, we have formed more than 30 different business relationships with pharmaceutical companies, biotechnology companies, research reagent and services companies, the federal government, and medical research foundations. Those partnerships have generated approximately over $1.5 billion in realized funding to date, enabling investment in our platform and our product pipeline.